The evidence for the benefits from breast milk in the neurodevelopment of premature babies – a review of the recent literature

Introduction. The brain in preterm babies is usually not fully developed and therefore early post-term events can have long-lasting neurodevelopment and cognitive outcomes. It is known that cerebral white matter connectivity is important for later intact cognitive functioning amongst children born very preterm and that breast milk imparts neurotrophic factors. The relationship between breastfeeding and child development is a long and well-studied area, and the evidence in support of breast milk is already substantial. Here we review the recent literature on the topic to establish whether additional evidence is available to strengthen the view that breast milk is superior in maximizing neurological development in premature infants. Materials and Methods. A search was undertaken of PubMed, limited to the last 10 years and humans. No language restrictions were imposed. Results. The search yielded 45 articles, of which 12 included all three elements of breast milk, neurological/cognitive development and preterm babies; 10 were reviewed. The gestation period and birth weight (either or both were reported) ranged from 23 to 36 weeks and from 580g t

Human metabolic adaptations and prolonged expensive neurodevelopment: A review

1.	After weaning, human hunter-gatherer juveniles receive substantial (≈3.5-7 MJ day^-1^), extended (≈15 years) and reliable (kin and nonkin food pooling) energy provision.
2.	The childhood (pediatric) and the adult human brain takes a very high share of both basal metabolic rate (BMR) (child: 50-70%; adult: ≈20%) and total energy expenditure (TEE) (child: 30-50%; adult: ≈10%).
3.	The pediatric brain for an extended period (≈4-9 years-of-age) consumes roughly 50% more energy than the adult one, and after this, continues during adolescence, at a high but declining rate. Within the brain, childhood cerebral gray matter has an even higher 1.9 to 2.2-fold increased energy consumption. 
4.	This metabolic expensiveness is due to (i) the high cost of synapse activation (74% of brain energy expenditure in humans), combined with (ii), a prolonged period of exuberance in synapse numbers (up to double the number present in adults). Cognitive development during this period associates with volumetric changes in gray matter (expansion and contraction due to metabolic related size alterations in glial cells and capillary vascularization), and in white matter (expansion due to myelination). 
5.	Amongst mammals, anatomically modern humans show an unique pattern in which very slow musculoskeletal body growth is followed by a marked adolescent size/stature spurt. This pattern of growth contrasts with nonhuman primates that have a sustained fast juvenile growth with only a minor period of puberty acceleration. The existence of slow childhood growth in humans has been shown to date back to 160,000 BP. 
6.	Human children physiologically have a limited capacity to protect the brain from plasma glucose fluctuations and other metabolic disruptions. These can arise in adults, during prolonged strenuous exercise when skeletal muscle depletes plasma glucose, and produces other metabolic disruptions upon the brain (hypoxia, hyperthermia, dehydration and hyperammonemia). These are proportional to muscle mass.
7.	Children show specific adaptations to minimize such metabolic disturbances. (i) Due to slow body growth and resulting small body size, they have limited skeletal muscle mass. (ii) They show other adaptations such as an exercise specific preference for free fatty acid metabolism. (iii) While children are generally more active than adolescents and adults, they avoid physically prolonged intense exertion. 
8.	Childhood has a close relationship to high levels of energy provision and metabolic adaptations that support prolonged synaptic neurodevelopment. 
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Identification of long non-coding RNAs involved in neuronal development and intellectual disability

Recently, exome sequencing led to the identification of causal mutations in 16–31% of patients with intellectual disability (ID), leaving the underlying cause for many patients unidentified. In this context, the noncoding part of the human genome remains largely unexplored. For many long non-coding RNAs (lncRNAs) a crucial role in neurodevelopment and hence the human brain is anticipated. Here we aimed at identifying lncRNAs associated with neuronal development and ID. Therefore, we applied an integrated genomics approach, harnessing several public epigenetic datasets. We found that the presence of neuron-specific H3K4me3 confers the highest specificity for genes involved in neurodevelopment and ID. Based on the presence of this feature and GWAS hits for CNS disorders, we identified 53 candidate lncRNA genes. Extensive expression profiling on human brain samples and other tissues, followed by Gene Set Enrichment Analysis indicates that at least 24 of these lncRNAs are indeed implicated in processes such as synaptic transmission, nervous system development and neurogenesis. The bidirectional or antisense overlapping orientation relative to multiple coding genes involved in neuronal processes supports these results. In conclusion, we identified several lncRNA genes putatively involved in neurodevelopment and CNS disorders, providing a resource for functional studies

Neonatal Diagnostics: Toward Dynamic Growth Charts of Neuromotor Control

© 2016 Torres, Smith, Mistry, Brincker and Whyatt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).The current rise of neurodevelopmental disorders poses a critical need to detect risk early in order to rapidly intervene. One of the tools pediatricians use to track development is the standard growth chart. The growth charts are somewhat limited in predicting possible neurodevelopmental issues. They rely on linear models and assumptions of normality for physical growth data – obscuring key statistical information about possible neurodevelopmental risk in growth data that actually has accelerated, non-linear rates-of-change and variability encompassing skewed distributions. Here, we use new analytics to profile growth data from 36 newborn babies that were tracked longitudinally for 5 months. By switching to incremental (velocity-based) growth charts and combining these dynamic changes with underlying fluctuations in motor performance – as the transition from spontaneous random noise to a systematic signal – we demonstrate a method to detect very early stunting in the development of voluntary neuromotor control and to flag risk of neurodevelopmental derail.Peer reviewedFinal Published versio

Is exposure to secondhand smoke associated with cognitive parameters of children and adolescents?—a systematic literature review

PURPOSE: Despite the known association of second hand smoke (SHS) with increased risk of ill health and mortality, the effects of SHS exposure on cognitive functioning in children and adolescents are unclear. Through a critical review of the literature we sought to determine whether a relationship exists between these variables. METHODS: The authors systematically reviewed articles (dated 1989–2012) that investigated the association between SHS exposure (including in utero due to SHS exposure by pregnant women) and performance on neurocognitive and academic tests. Eligible studies were identified from searches of Web of Knowledge, MEDLINE, Science Direct, Google Scholar, CINAHL, EMBASE, Zetoc, and Clinicaltrials.gov. RESULTS: Fifteen articles were identified, of which 12 showed inverse relationships between SHS and cognitive parameters. Prenatal SHS exposure was inversely associated with neurodevelopmental outcomes in young children, whereas postnatal SHS exposure was associated with poor academic achievement and neurocognitive performance in older children and adolescents. Furthermore, SHS exposure was associated with an increased risk of neurodevelopmental delay. CONCLUSIONS: Recommendations should be made to the public to avoid sources of SHS and future research should investigate interactions between SHS exposure and other risk factors for delayed neurodevelopment and poor cognitive performance

Antibiotic use during pregnancy and neurodevelopmental outcomes of offspring in early childhood

There is limited research on the effects of antibiotic use during pregnancy on neurodevelopmental outcomes of offspring in early childhood. The aim of this study was to investigate associations between antibiotic use during early pregnancy and neurodevelopmental outcomes, both behavioral and cognitive, in the offspring during early childhood. This thesis examined a longitudinal study of 570 mother-child pairs where prenatal exposures and at least one neurodevelopment outcome assessment were recorded. An interview was conducted with mothers on average one year after delivery to collect information on prenatal exposures. Neurodevelopmental outcomes were assessed between the ages 5–11 years using the cognitive-based outcomes of Peabody Picture Vocabulary Test (PPVT-III) and the Beery-Buktenica Test of Visual Motor Integration-Fifth Edition (VMI-5) and behavioral-based outcomes of the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF). Adjusted mean differences (adjMD) in outcome measures were calculated between mothers reporting antibiotics use and mothers reporting treated infections. Antibiotic use during pregnancy was not significantly associated with the two cognitive measures but was associated with increased total behavioral problems reported by mothers (adjMD: 2.60; CI: 0.50, 4.69) and teachers (adjMD 2.60; 95% CI 0.44, 4.76). Overall, antibiotics use during pregnancy was not associated with differences in childhood cognition but may be associated with greater behavior problems

Breastfeeding, the use of docosahexaenoic acid-fortified formulas in infancy and neuropsychological function in childhood

OBJECTIVE: To investigate the relation between breastfeeding, use of docosahexaenoic acid (DHA)-fortified formula and neuropsychological function in children. DESIGN: Prospective cohort study. SETTING: Southampton, UK. SUBJECTS: 241 children aged 4 years followed up from birth. MAIN OUTCOME MEASURES: IQ measured by the Wechsler Pre-School and Primary Scale of Intelligence (3rd edn), visual attention, visuomotor precision, sentence repetition and verbal fluency measured by the NEPSY, and visual form-constancy measured by the Test of Visual-Perceptual Skills (Non-Motor). RESULTS: In unadjusted analyses, children for whom breast milk or DHA-fortified formula was the main method of feeding throughout the first 6 months of life had higher mean full-scale and verbal IQ scores at age 4 years than those fed mainly unfortified formula. After adjustment for potential confounding factors, particularly maternal IQ and educational attainment, the differences in IQ between children in the breast milk and unfortified formula groups were severely attenuated, but children who were fed DHA-fortified formula had full-scale and verbal IQ scores that were respectively 5.62 (0.98 to 10.2) and 7.02 (1.56 to 12.4) points higher than children fed unfortified formula. However, estimated total intake of DHA in milk up to age 6 months was not associated with subsequent IQ or with score on any other test. CONCLUSIONS: Differences in children's intelligence according to type of milk fed in infancy may be due more to confounding by maternal or family characteristics than to the amount of long-chain polyunsaturated fatty acids they receive in milk

Brain organoids and insights on human evolution.

Human brain organoids, generated from pluripotent stem cells, have emerged as a promising technique for modeling early stages of human neurodevelopment in controlled laboratory conditions. Although the applications for disease modeling in a dish have become routine, the use of these brain organoids as evolutionary tools is only now getting momentum. Here, we will review the current state of the art on the use of brain organoids from different species and the molecular and cellular insights generated from these studies. Besides, we will discuss how this model might be beneficial for human health and the limitations and future perspectives of this technology